Pramlintide is the first new antihyperglycemic agent approved for both type 2 and type 1 diabetes since insulin was developed in the 1920s. It is a synthetic analogue of human amylin, a naturally occurring neuroendocrine hormone synthesized by pancreatic beta cells. Pramlintide helps regulate the rate of glucose appearance and improves glucose control postprandially. This action is accomplished through suppressing inappropriate postprandial glucagon secretion and regulating gastric emptying, and is associated with a feeling of satiety. It is given at mealtimes and is indicated for use in type 2 and type 1 diabetes as an adjunct treatment in patients who use mealtime insulin therapy and who have failed to achieve desired glucose control despite optimal insulin therapy. Pramlintide therapy should only be considered for patients who are receiving ongoing care under the guidance of a health care professional skilled in the use of insulin and supported by services of diabetes educators. Pramlintide is used with insulin and has been associated with an increased risk of insulin-induced severe hypoglycemia, particularly in type 1 diabetes. Appropriate patient selection, careful patient instruction, and insulin dose adjustments help reduce this risk. In type 2 diabetes, pramlintide is initiated at 60 microg and may be increased to 120 microg two to three times daily with meals. In type 1 diabetes, pramlintide is initiated at 15 microg and may be increased to 30 or 60 microg with meals. Mealtime insulin should be reduced by 50% at pramlintide initiation and adjusted as the pramlintide dose is increased. It should be given subcutaneously with an insulin syringe and should not be mixed with insulin. The most commonly reported side effect is mild to moderate nausea with initiation, which is usually transient and short term in nature. Frequent self-monitoring of blood glucose is important during initiation to assist in insulin adjustments. Insulin type, dose, and timing as well as basal/bolus balance may require adjustment during pramlintide initiation. Despite requiring additional injections, patients report satisfaction with pramlintide therapy.